Wang, Xin (2018) Understanding genetic and epigenetic factors in cell-type and condition-specific gene regulation. PhD thesis, Victor Chang Cardiac Research Institute & St Vincent's Clinical School, Faculty of Medicine, UNSW.
Preview |
Text
2018 Xin Wang_PhD Thesis.pdf Download (8MB) | Preview |
Abstract
One of the biggest mysteries in modern molecular biology is how can the same genomic DNA sequence that is present in all cells in a multi-cellular organism express different genes in different cell-types and conditions. In this PhD thesis, I present novel bioinformatics methods and apply them to large functional genomic data sets to unravel some of the genetic and epigenetic determinants of cell-type and condition-specific gene regulation in eukaryotic organisms. The key contributions of this thesis include: 1. Demonstrating that combinations of transcription factor (TF) motifs alone can be predictive of cell-type-specific TF binding: I developed and used a new motif annotation and analysis pipeline to screen ENCODE TF ChIP-seq datasets to identify cell-type-specific motif combinations in different cell lines. Furthermore, I was able to extract the underlying rules, or TF grammar, that is predictive of cell-type specificity. 2. Charting the genome-wide chromatin state map of a filamentous fungus Aspergillus nidulans and discovering how changes in environmental nutrient affect the chromatin state and gene expression: I applied state-of-the-art bioinformatics methods to jointly infer an 11-state chromatin landscape of A. nidulans in a nitrogen-rich and a nitrogen-free condition. My analysis identified and characterised nitrogen-responsive and non-responsive chromatin, how they influence downstream gene expression and the association with different functional categories of genes. In particular, I found two new chromatin states that are enriched for secondary metabolism (SM) gene clusters. Furthermore, SM genes have an increase of H3K9me3 upon nitrogen depletion suggesting that SM genes are potentially being further repressed, which is consistent with the observation that these genes should remain silent in this starvation condition. Our results contribute to new understanding of condition-specific gene regulation in A. nidulans and have implication to understanding gene regulation in other eukaryotic
| Item Type: | Thesis (PhD ) |
|---|---|
| Additional Information: | SUPERVISORS: Ho, Joshua W.K., Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW; Suter, Catherine, Victor Chang Cardiac Research Institute, Faculty of Medicine, UNSW; Wong, Koon Ho, University of Macau. THESIS UNDER EMBARGO UNTIL SEP 2020. |
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 16 Apr 2019 23:53 |
| Last Modified: | 16 Oct 2020 01:08 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/830 |
Actions (login required)
 |
View Item |